Multiple domain insertions and losses in the evolution of the Rab prenylation complex

BackgroundRab proteins are regulators of vesicular trafficking, requiring a lipid modification for proper function, prenylation of C-terminal cysteines. This is catalysed by a complex of a catalytic heterodimer (Rab Geranylgeranyl Transferase – RabGGTase) and an accessory protein (Rab Escort Protein. REP). Components of this complex display domain insertions relative to paralogous proteins. The function of these inserted domains is unclear.ResultsWe profiled the domain architecture of the components of the Rab prenylation complex in evolution. We identified the orthologues of the components of the Rab prenylation machinery in 43 organisms, representing the crown eukaryotic groups. We characterize in detail the domain structure of all these components and the phylogenetic relationships between the individual domains.ConclusionWe found different domain insertions in different taxa, in α-subunits of RGGTase and REP. Our results suggest that there were multiple insertions, expansions and contractions in the evolution of this prenylation complex.

[1]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[2]  S. Maurer-Stroh,et al.  Protein Prenyltransferases: Anchor Size, Pseudogenes and Parasites , 2003, Biological chemistry.

[3]  Geoffrey J. Barton,et al.  The Jalview Java alignment editor , 2004, Bioinform..

[4]  W. Balch,et al.  Organization of the Rab‐GDI/CHM Superfamily: The Functional Basis for Choroideremia Disease , 2001, Traffic.

[5]  M S Waterman,et al.  Identification of common molecular subsequences. , 1981, Journal of molecular biology.

[6]  S. Baldauf,et al.  The Deep Roots of Eukaryotes , 2003, Science.

[7]  S. Ramachandran,et al.  Comparative and evolutionary analysis of genes encoding small GTPases and their activating proteins in eukaryotic genomes. , 2006, Physiological genomics.

[8]  I. Wilson,et al.  Structural insights into the function of the Rab GDI superfamily. , 1996, Trends in biochemical sciences.

[9]  N. Grishin,et al.  The α‐subunit of protein prenyltransferases is a member of the tetratricopeptide repeat family , 1999, Protein science : a publication of the Protein Society.

[10]  J. Pereira-Leal,et al.  Evolution of the Rab family of small GTP-binding proteins. , 2001, Journal of molecular biology.

[11]  A G Murzin,et al.  SCOP: a structural classification of proteins database for the investigation of sequences and structures. , 1995, Journal of molecular biology.

[12]  Tim J. P. Hubbard,et al.  SCOP database in 2004: refinements integrate structure and sequence family data , 2004, Nucleic Acids Res..

[13]  H. Dyson,et al.  Intrinsically unstructured proteins and their functions , 2005, Nature Reviews Molecular Cell Biology.

[14]  S. Ferro-Novick,et al.  Identification of yeast component A: reconstitution of the geranylgeranyltransferase that modifies Ypt1p and Sec4p. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[15]  John P. Huelsenbeck,et al.  MRBAYES: Bayesian inference of phylogenetic trees , 2001, Bioinform..

[16]  Sonia Longhi,et al.  Assessing protein disorder and induced folding , 2005, Proteins.

[17]  Herbert Waldmann,et al.  Structure of Rab escort protein-1 in complex with Rab geranylgeranyltransferase. , 2003, Molecules and Cells.

[18]  Robert D. Finn,et al.  iPfam: visualization of protein?Cprotein interactions in PDB at domain and amino acid resolutions , 2005, Bioinform..

[19]  Jonathan A. Eisen,et al.  The age of the Arabidopsis thaliana genome duplication , 2003, Plant Molecular Biology.

[20]  Cyrus Chothia,et al.  The SUPERFAMILY database in 2004: additions and improvements , 2004, Nucleic Acids Res..

[21]  Christopher J. Oldfield,et al.  Functional anthology of intrinsic disorder. 3. Ligands, post-translational modifications, and diseases associated with intrinsically disordered proteins. , 2007, Journal of proteome research.

[22]  I. Longden,et al.  EMBOSS: the European Molecular Biology Open Software Suite. , 2000, Trends in genetics : TIG.

[23]  C. Benes,et al.  The C2 domain of PKCdelta is a phosphotyrosine binding domain. , 2005, Cell.

[24]  J. Pereira-Leal,et al.  Prenylation of Rab GTPases: molecular mechanisms and involvement in genetic disease , 2001, FEBS letters.

[25]  B. Kobe,et al.  The leucine-rich repeat as a protein recognition motif. , 2001, Current opinion in structural biology.

[26]  H. Innan,et al.  Selection for more of the same product as a force to enhance concerted evolution of duplicated genes. , 2006, Trends in genetics : TIG.

[27]  S. J. McTaggart,et al.  Isoprenylated proteins , 2005, Cellular and Molecular Life Sciences CMLS.

[28]  Sarah A Teichmann,et al.  Evolution of protein complexes by duplication of homomeric interactions , 2007, Genome Biology.

[29]  Tim Hubbard,et al.  Domain insertions in protein structures. , 2004, Journal of molecular biology.

[30]  J Deisenhofer,et al.  Crystal structure of Rab geranylgeranyltransferase at 2.0 A resolution. , 2000, Structure.

[31]  I. Moore,et al.  The Arabidopsis Rab GTPase family: another enigma variation. , 2002, Current opinion in plant biology.

[32]  Janusz M Bujnicki,et al.  Sequence permutations in the molecular evolution of DNA methyltransferases , 2002, BMC Evolutionary Biology.

[33]  I. Wilson,et al.  Structure and mutational analysis of Rab GDP-dissociation inhibitor , 1996, Nature.

[34]  J. Falke,et al.  The C2 domain calcium‐binding motif: Structural and functional diversity , 1996, Protein science : a publication of the Protein Society.

[35]  R. Baron,et al.  Thematic review series: Lipid Posttranslational Modifications. Geranylgeranylation of Rab GTPases Published, JLR Papers in Press, January 9, 2006. , 2006, Journal of Lipid Research.

[36]  S. Henikoff,et al.  Amino acid substitution matrices from protein blocks. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[37]  S. Ferro-Novick,et al.  Bet2p and Mad2p are components of a prenyltransferase that adds geranylgeranyl onto Ypt1p and Sec4p , 1993, Nature.

[38]  Sarah A Teichmann,et al.  Relative rates of gene fusion and fission in multi-domain proteins. , 2005, Trends in genetics : TIG.

[39]  E. Bornberg-Bauer,et al.  Domain deletions and substitutions in the modular protein evolution , 2006, The FEBS journal.

[40]  Sebastian Maurer-Stroh,et al.  Protein prenyltransferases , 2003, Genome Biology.

[41]  C. Ponting,et al.  Protein repeats: structures, functions, and evolution. , 2001, Journal of structural biology.

[42]  Christopher J. Oldfield,et al.  Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions. , 2007, Journal of proteome research.

[43]  P. Casey,et al.  Crystal Structure of Protein Farnesyltransferase at 2.25 Angstrom Resolution , 1997, Science.

[44]  B. Larijani,et al.  Multiple Factors Contribute to Inefficient Prenylation of Rab27a in Rab Prenylation Diseases* , 2003, Journal of Biological Chemistry.

[45]  P. Casey,et al.  Structure of mammalian protein geranylgeranyltransferase type‐I , 2003, The EMBO journal.

[46]  Frances M. G. Pearl,et al.  The CATH Domain Structure Database and related resources Gene3D and DHS provide comprehensive domain family information for genome analysis , 2004, Nucleic Acids Res..

[47]  John P. Huelsenbeck,et al.  MrBayes 3: Bayesian phylogenetic inference under mixed models , 2003, Bioinform..

[48]  G. Schulz,et al.  Structure and function of a squalene cyclase. , 1997, Science.

[49]  W. Balch,et al.  Molecular Basis for Rab Prenylation , 2000, The Journal of cell biology.

[50]  T. Südhof,et al.  Evolutionarily Conserved Multiple C2 Domain Proteins with Two Transmembrane Regions (MCTPs) and Unusual Ca2+ Binding Properties* , 2005, Journal of Biological Chemistry.

[51]  E. Bornberg-Bauer,et al.  Evolution of circular permutations in multidomain proteins. , 2006, Molecular biology and evolution.

[52]  J. Bonifacino,et al.  Adaptins: the final recount. , 2001, Molecular biology of the cell.

[53]  G J Barton,et al.  Application of multiple sequence alignment profiles to improve protein secondary structure prediction , 2000, Proteins.

[54]  Cyrus Chothia,et al.  SUPERFAMILY: HMMs representing all proteins of known structure. SCOP sequence searches, alignments and genome assignments , 2002, Nucleic Acids Res..

[55]  V. Uversky.  Natively unfolded proteins: A point where biology waits for physics , 2002, Protein science : a publication of the Protein Society.

[56]  Cyrus Chothia,et al.  The SUPERFAMILY database in 2007: families and functions , 2006, Nucleic Acids Res..

[57]  R. Russell,et al.  Domain insertion. , 1994, Protein engineering.

[58]  L. Beese,et al.  Thematic review series: Lipid Posttranslational Modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I Published, JLR Papers in Press, February 13, 2006. , 2006, Journal of Lipid Research.

[59]  Julian Gough,et al.  Convergent evolution of domain architectures (is rare) , 2005, Bioinform..

[60]  R. Veitia,et al.  Nonlinear effects in macromolecular assembly and dosage sensitivity. , 2003, Journal of theoretical biology.

[61]  Robert B. Russell,et al.  GlobPlot: exploring protein sequences for globularity and disorder , 2003, Nucleic Acids Res..

[62]  Geoffrey J. Barton,et al.  JPred : a consensus secondary structure prediction server , 1999 .

[63]  C. Pál,et al.  Dosage sensitivity and the evolution of gene families in yeast , 2003, Nature.

[64]  S. Powers,et al.  RAM2, an essential gene of yeast, and RAM1 encode the two polypeptide components of the farnesyltransferase that prenylates a-factor and Ras proteins. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[65]  Sarah A Teichmann,et al.  Novel specificities emerge by stepwise duplication of functional modules. , 2005, Genome research.

[66]  Matteo Pellegrini,et al.  Detection of parallel functional modules by comparative analysis of genome sequences , 2005, Nature Biotechnology.

[67]  C. Benes,et al.  The C2 Domain of PKCδ Is a Phosphotyrosine Binding Domain , 2005, Cell.

[68]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[69]  S. Teichmann,et al.  The relationship between domain duplication and recombination. , 2005, Journal of molecular biology.